TXNIP/p-PRKAA promotes ferroptosis through the BECN1/SLC7A11 signaling pathway in intestinal ischemia/reperfusion injury

Ferroptosis has emerged as a key player in intestinal ischemia/reperfusion (I/R) injury. Although BECN1 has been recognized as a crucial factor in the progression of I/R injury, its role in ferroptosis during intestinal I/R injury is still inadequately understood. In this study, we established an in vivo model of intestinal I/R injury and an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) in Caco-2 cells. Our findings indicated that ferroptosis significantly contributed to the aggravation of intestinal tissue damage and cellular death. BECN1 expression levels were increased. By overexpressing or silencing BECN1, it was observed that activated BECN1 promotes ferroptosis during OGD/R by targeting SLC7A11. Furthermore, TXNIP/p-PRKAA regulates ferroptosis during I/R through the BECN1/SLC7A11 pathway. Finally, in vivo TXNIP knockout inhibited ferroptosis and attenuated intestinal I/R injury through the BECN1/SLC7A11 pathway. To summarize, this research highlights the critical role of TXNIP/p-PRKAA in modulating ferroptosis through its interaction with BECN1/SLC7A11. TXNIP and BECN1 are potential therapeutic treatment targets.